Forkhead box L2 is a target of miR-133b and plays an important role in the pathogenesis of non-small cell lung cancer

Abstract

Background: Forkhead box L2 (FOXL2) has been recognized as a transcription factor in the progression of many malignancies, but its role in non-small cell lung cancer (NSCLC) remains unclear. This research clarified on the role of FOXL2 and the specific molecular mechanism in NSCLC.

Methods: RNA and protein levels were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting assays. Cell proliferation was examined by cell counting kit-8 (CCK-8) and clonogenic assays. Transwell and wound healing assays were used to detect cell invasion and migration. Cell cycle alterations were assessed by flow cytometry. The relationship between FOXL2 and miR-133b was verified by dual-luciferase reporter assays. In vivo metastasis was monitored in the tail vein-injected mice.

Results: FOXL2 was upregulated in NSCLC cells and tissues. Downregulation of FOXL2 restrained cell proliferation, migration, and invasion and arrested the cell cycle of NSCLC cells. Moreover, FOXL2 promoted the epithelial-mesenchymal transition (EMT) process of NSCLC cells by inducing the transforming growth factor-β (TGF-β)/Smad signaling pathway. miR-133b directly targeted the 3'-UTR of FOXL2 and negatively regulated FOXL2 expression. Knockdown of FOXL2 blocked metastasis in vivo.

Conclusions: miR-133b downregulates FOXL2 by targeting the 3'-UTR of FOXL2, thereby inhibiting cell proliferation, EMT and metastasis induced by the TGF-β/Smad signaling pathway in NSCLC. FOXL2 may be a potential molecular target for treating NSCLC.

Keywords: TGF-β/Smad signaling; carcinoma, non-small-cell lung cancer (NSCLC); epithelial-mesenchymal transition (EMT); forkhead box protein L2 (FOXL2); miR-133b.